The influence of solvent on peptide conformation is to be investigated, with particular emphasis on differences between aqueous and organic evnironments. (a) Conformational equilibria of a series of cyclic peptides that occur in two known backbone conformations will be studied by nuclear magnetic resonance to extract the enthalpy and entropy changes for the transition. These parameters will be obtained as a function of solvent and side chain substitution, so that contributions of the solvation of individual groups in the two conformational states may be identified. (b) X-ray crystallographic analysis of these cyclic peptides and other peptide crystals likely to contain water will be determined. (c) Data from these crystals and published data from other crystals of hydrated peptides will be analyzed to identify likely modes of peptide hydration. (d) Models of peptide hydration in solution will be developed from the data collected and tested in their predictions of the effect of water, as distinguished from organic solvents, on the conformations of flexible (acyclic) peptides, including hormones and neuropeptides. An ability to predict differences in conformation between aqueous and non-aqueous environments may be of use in design of pharmacologically useful peptides, as well as in prediction of protein chain folding from amino acid sequence.